{"title":"Protocatechuic acid suppresses ferroptosis to protect against hypoxic-ischemic encephalopathy by targeting the HIF-1α/VEGFA axis","authors":"Xiaoling Zhang , Jingjing Luo , Laxman Bharati , Ziyu Hua , Sha Chen , Zhi Dong","doi":"10.1016/j.phymed.2025.156900","DOIUrl":"10.1016/j.phymed.2025.156900","url":null,"abstract":"<div><h3>Background</h3><div>Patients with Hypoxic–ischemic encephalopathy (HIE) face substantial risks of poor neurological outcomes and fatal complications, imposing a substantial clinical burden. Protocatechuic acid (PCA), a safe, water-soluble antioxidant with demonstrated neuroprotective properties, has emerged as a promising perinatal therapeutic candidate. However, its mechanisms of action in HIE remain poorly understood. Notably, previous research on HIE has primarily focused on neuronal cells, with limited attention paid to its effects on endothelial cells. Our study emphasizes the role of PCA in cerebral endothelial cells and the subsequent impact of the altered microenvironment on neuronal cells, which may provide a novel therapeutic strategy for HIE.</div></div><div><h3>Purpose</h3><div>Our subject discuss the role and mechanisms of PCA in HIE.</div></div><div><h3>Study design</h3><div>This study observed that PCA exhibits a mitigating effect on HIE, prompting further investigation. Utilizing network pharmacology and RNA sequencing analysis, we elucidated the pathways through which PCA exerts its effects on HIE. Subsequently, we conducted verification using animal and cellular models.</div></div><div><h3>Methods</h3><div>The Rice-Vannucci technique was used to generate neonatal HIE, and Bend. 3 cells were used to create an oxygen–glucose deprivation/reoxygenation (OGD/R) model. To clarify the neuroprotective mechanisms of PCA, a thorough multidisciplinary approach was used, including network pharmacology, RNA sequencing, TTC staining, behavioral evaluations, western blotting, and immunofluorescence.</div></div><div><h3>Results</h3><div>The results showed that PCA helps prevent ferroptosis and reduces damage caused by HIE, suggesting it could be a useful treatment in medicine. In vivo, PCA improved neurological outcomes, reduced the infarct volume, and alleviated HIE-related pathological changes by enhancing VEGFA nuclear translocation and activating the hypoxia-inducible factor 1-alpha (HIF-1α)/VEGFA signaling pathway in cerebrovascular endothelial cells. In vitro, PCA suppressed oxidative stress and ferroptosis marker levels, effects that were reversed by the HIF-1α inhibitor PX-478, and co-culture with neuronal cells alleviated OGD/R-induced neuronal confirming the critical role of this pathway in PCA-mediated neuroprotection.</div></div><div><h3>Conclusion</h3><div>In conclusion, PCA confers robust protection against ferroptosis-mediated damage in HIE, with its neuroprotective effects mechanistically linked to the regulation of ferroptosis through the HIF-1α/VEGFA axis in brain microvascular endothelial cells. Moreover, PCA-modified endothelial cell microenvironment ameliorates neuronal damage following injury. These results highlight PCA's therapeutic potential and lay the groundwork for additional translational studies.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156900"},"PeriodicalIF":6.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PhytomedicinePub Date : 2025-05-23DOI: 10.1016/j.phymed.2025.156726
Yina Yu , Haoyang Hu , Yichun Zhang , Zhijuan Zhang , Shuaibing Ying , Shaohua Dong , Jinyao Dai , Yuqi Hong , Yunqing Qiu , Yan Lou
{"title":"Hedyotis chrysotricha aqueous extract inhibits hepatitis B surface antigen and viral replication via hepatocyte nuclear factor 4α regulation","authors":"Yina Yu , Haoyang Hu , Yichun Zhang , Zhijuan Zhang , Shuaibing Ying , Shaohua Dong , Jinyao Dai , Yuqi Hong , Yunqing Qiu , Yan Lou","doi":"10.1016/j.phymed.2025.156726","DOIUrl":"10.1016/j.phymed.2025.156726","url":null,"abstract":"<div><h3>Background</h3><div>Chronic hepatitis B virus (HBV) infection continues to pose a significant global public health challenge, as current antiviral treatments have not yet succeeded in completely eradicating the virus. Traditional Chinese Medicine (TCM) offers unique advantages in treating chronic hepatitis B. Furthermore, the aqueous extract of <em>Hedyotis chrysotricha</em> (Palib.) Merr (HCM), a synonym of <em>Exallage chrysotricha</em> (Palib.) Neupane & N.Wikstr., has shown potential anti-HBV properties. Nevertheless, its pharmacological effects and precise mechanisms of action remain unclear.</div></div><div><h3>Purpose</h3><div>We aim to evaluate the anti-HBV efficacy of the aqueous extract of HCM and investigate its underlying mechanisms.</div></div><div><h3>Study design</h3><div>Ultra performance liquid chromatography-triple time-of-flight mass spectrometry (UPLC-Triple-TOF/MS) was used to identify the HCM components, and the anti-HBV efficacy of HCM was evaluated using a transgenic HBV mouse model, as well as the HepG2.2.15 and HepAD38 HBV cell lines.</div></div><div><h3>Methods</h3><div>We first identified the chemical components of HCM using UPLC-Triple-TOF/MS, combined with relevant reference standards. Quantification was achieved using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), followed by methodology validation. We used a transgenic HBV mouse model along with the HepG2.2.15 and HepAD38 HBV cell lines to assess its anti-HBV efficacy. Besides, network pharmacology, molecular docking and transcriptomics were employed to explore the underlying anti-HBV mechanisms.</div></div><div><h3>Results</h3><div>UPLC analysis, using authentic reference standards, identified 19 major chemical components in HCM, including isorhamnetin, monotropein, sesamoside, and kaempferol, which were newly identified as components in this matrix. Our study demonstrates that HCM significantly inhibited HBV replication and transcription in both the transgenic HBV mouse model and HBV cell lines, with a notable reduction in HBsAg levels and the potential inhibition of cccDNA, which serves as a stable viral DNA reservoir in the nucleus of infected hepatocytes, driving the replication and persistence of HBV. Further analysis using network pharmacology and transcriptomic approaches suggests that the anti-hepatitis B mechanism may involve the upregulation of the phosphatidylinositol 3-kinase - protein kinase B (PI3K-AKT) and mitogen-activated protein kinase - extracellular signal-regulated kinase 1 and 2 (MAPK-ERK1/2) pathways. Additionally, hepatocyte nuclear factor 4α (HNF4α) was shown to play a critical role in HBV inhibition, with its function negatively regulated by the PI3K-AKT and MAPK-ERK1/2 pathways.</div></div><div><h3>Conclusion</h3><div>The aqueous extract of HCM not only inhibits HBV replication and transcription but also significantly suppresses HBsAg levels. The underlying mechanism likely involves the concurr","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156726"},"PeriodicalIF":6.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PhytomedicinePub Date : 2025-05-22DOI: 10.1016/j.phymed.2025.156885
Zhenchuan Liu , Fei Qiao , Dejian Liu , Xiangzhen Kong , Kaiwen Liu , Hanwen Gu , Yuanqiang Zhang , Qunbo Meng , Lei Cheng
{"title":"Periplocin targets LRP4 to regulate metabolic homeostasis and anti-inflammation for the treatment of IVDD","authors":"Zhenchuan Liu , Fei Qiao , Dejian Liu , Xiangzhen Kong , Kaiwen Liu , Hanwen Gu , Yuanqiang Zhang , Qunbo Meng , Lei Cheng","doi":"10.1016/j.phymed.2025.156885","DOIUrl":"10.1016/j.phymed.2025.156885","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration (IVDD) is characterized by deteriorating intervertebral discs, leading primarily to low back pain and leg pain. Most current treatments for IVDD primarily address symptoms without targeting the underlying degenerative process. Moreover, tumor necrosis factor-α (TNF-α)-mediated inflammation and degradation of the nucleus pulposus (NP) extracellular matrix (ECM) influence this pathological process. Periplocin, a cardiotonic steroid extracted from <em>periplocin forrestii</em>, has demonstrated a wide range of medical benefits, including cardiotonic, anticancer, anti-inflammatory, and wound healing properties. Nevertheless, the effects of periplocin on IVDD remain unexplored.</div></div><div><h3>Objective</h3><div>Our study explores the mechanism of action and the potential target of periplocin in mitigating IVDD pathology.</div></div><div><h3>Methods</h3><div>Rat models of IVDD were established using acupuncture, and the affected discs underwent analysis via Safranin O-Fast Green (S-O) and Hematoxylin and Eosin (H&E) staining. Nucleus pulposus cells (NPCs) were harvested from IVDD patients and experimental animals for examination. A variety of techniques, including Western blot analysis, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) assay, immunofluorescence staining, Alcian Blue staining and Immunohistochemistry (IHC) staining, were utilized to evaluate inflammation-related proteins, mRNAs and the ECM metabolism. In order to ascertain the potential protein targets of periplocin, the binding site of periplocin to LRP4 was elucidated through the utilisation of molecular docking experiments. Subsequently, the expression of low-density lipoprotein receptor-related protein 4 (LRP4) in NPCs was modified through the use of small interfering RNA (siRNA) knockdown and overexpression vectors, which were employed for the purposes of target validation.</div></div><div><h3>Results</h3><div>We conclude from the present study that periplocin alleviates the progression of IVDD mainly through the following aspects: periplocin inhibits TNF-α-induced inflammatory; periplocin reduces matrix degradation; periplocin promotes matrix anabolism and regulates metabolic homeostasis. Moreover, the present study demonstrates that LRP4 is involved as a potential target in the multiple pathways mentioned above to protect the intervertebral disc.</div></div><div><h3>Conclusion</h3><div>Our research suggests that periplocin may serve as a promising treatment for IVDD, offering anti-inflammatory benefits, preventing ECM degradation, and promoting ECM anabolism.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156885"},"PeriodicalIF":6.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PhytomedicinePub Date : 2025-05-21DOI: 10.1016/j.phymed.2025.156879
XiaoMing Zhou , ChenXi Zhang , Wen Shen , RuiFei Zhuang , ShenLin Liu , JinDi Liu
{"title":"Curzerene suppresses epithelial-mesenchymal transition in gastric precancerous lesion cells through targeted regulation of YAP via the long non-coding RNA AFAP1-AS1","authors":"XiaoMing Zhou , ChenXi Zhang , Wen Shen , RuiFei Zhuang , ShenLin Liu , JinDi Liu","doi":"10.1016/j.phymed.2025.156879","DOIUrl":"10.1016/j.phymed.2025.156879","url":null,"abstract":"<div><h3>Background</h3><div>Curzerene, a bioactive compound from Curcuma zedoaria, exhibits anticancer effects, but its role in gastric precancerous lesions remains poorly understood. This study investigates the potential of Curzerene in inhibiting gastric precancerous lesions progression by regulating the long non-coding RNA (LncRNA) AFAP1-AS1 and the Hippo/YAP signaling pathway.</div></div><div><h3>Methods</h3><div>In vitro, a gastric precancerous cell model (MC cells) was established by treating GES-1 cells with MNNG. The effects of Curzerene on cell proliferation, migration, and EMT were assessed using CCK-8, scratch assays, RT-PCR, and Western blot. In vivo, a gastric precancerous mouse model was induced by MNU, and the therapeutic effects of Curzerene (14 mg/kg and 28 mg/kg) were evaluated through histological and molecular analysis.</div></div><div><h3>Results</h3><div>Curzerene treatment significantly inhibited MC cell proliferation, migration, and EMT, downregulating LncRNA AFAP1-AS1 and YAP while upregulating E-cadherin and downregulating N-cadherin. In vivo, Curzerene alleviated gastric mucosal damage, reduced cancer markers (P53 and CD133), and improved histopathology. Transcriptomic analysis identified the Hippo/YAP pathway as a key mediator of Curzerene’s effects. YAP activation reversed Curzerene’s inhibitory effects on EMT, confirming the involvement of this pathway.</div></div><div><h3>Conclusion</h3><div>Curzerene effectively inhibits gastric precancerous lesion progression by targeting the YAP signaling and the following LncRNA AFAP1-AS1 to suppress EMT. These findings suggest Curzerene’s novel potential as a promising therapeutic agent for early intervention and prevention of gastric cancer.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156879"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PhytomedicinePub Date : 2025-05-21DOI: 10.1016/j.phymed.2025.156870
Wencheng Wei , Hao Wang , Li Fu , Hui Liu
{"title":"Icaritin induces paraptosis in hepatocellular carcinoma cells by targeting BHLHE40 via endoplasmic reticulum stress and mitochondrial dysfunction","authors":"Wencheng Wei , Hao Wang , Li Fu , Hui Liu","doi":"10.1016/j.phymed.2025.156870","DOIUrl":"10.1016/j.phymed.2025.156870","url":null,"abstract":"<div><h3>Objective</h3><div>Icaritin, a flavonoid derived from the traditional Chinese medicine <em>Epimedium</em>, exhibits diverse biological activities; however, the mechanisms underlying its effects against hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate the anticancer properties of icaritin and elucidate the mechanisms of icaritin-induced cell death.</div></div><div><h3>Methods</h3><div>The effects of icaritin-induced paraptosis were assessed using CellTiter-Glo, EdU, and colony formation assays, and phenotypic observations. Transcriptome analysis was performed to identify the dysregulated genes associated with icaritin-induced paraptosis. Western blotting and qRT-PCR were used to analyze icaritin-induced changes in protein and mRNA levels, respectively. Mito-GFP, ROS, and MMP assays were conducted to monitor the mitochondrial status. IPA, molecular docking, CETSA, shRNA and cell-derived xenografts confirmed the role of <em>BHLHE40</em> in icaritin-induced paraptosis <em>in vivo</em> and <em>in vitro</em></div></div><div><h3>Results</h3><div>Icaritin induced paraptosis in HCC cells, which was characterized by cytoplasmic vacuolation and caspase-independent. Transcriptomic analysis indicated that icaritin triggered ER stress and mitochondrial dysfunction, validated by molecular and biochemical assays. IPA, molecular docking, and CETSA analyses identified <em>BHLHE40</em> as a crucial mediator of this process. <em>BHLHE40</em> knockdown inhibited ER stress and mitochondrial dysfunction, significantly reducing icaritin-induced paraptosis in HCC cells. Animal experiments demonstrated that silencing of <em>BHLHE40</em> diminished the inhibitory effects of icaritin on tumor growth in xenograft models.</div></div><div><h3>Conclusion</h3><div>These results highlight the potent anticancer effects of icaritin, particularly its ability to induce paraptosis by targeting <em>BHLHE40</em>. This study provides a comprehensive understanding of the anticancer mechanisms of icaritin and suggests that targeting <em>BHLHE40</em> represents a novel therapeutic strategy for enhancing the efficacy of cancer treatment.</div></div><div><h3>Abbreviations</h3><div>HCC: Hepatocellular carcinoma; TCM: Traditional Chinese Medicine; ER: Endoplasmic Reticulum; MMP: Mitochondrial Membrane Potential; ROS: Reactive Oxygen Species; CTG: CellTiter-Glo; EdU: 5-ethynyl-2′-deoxyuridine; UPR: Unfolded Protein Response; BHLHE40: Basic helix-loop-helix family member E40; IPA: Ingenuity Pathway Analysis; CETSA: Cellular Thermal Shift Assay; PI: Propidium Iodide;PCR: Polymerase Chain Reaction; qRT-PCR: Quantitative Reverse Transcription PCR; GFP: Green Fluorescent Protein; JC-1: 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide; ATF4: Activating Transcription Factor 4; PERK: Protein kinase RNA-like ER kinase; DDIT3: DNA Damage Inducible Transcript 3; LMNA: Lamin A/C; IC50: Half Maximal Inhibitory Concentration; PEG300: Polyethyle","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156870"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PhytomedicinePub Date : 2025-05-21DOI: 10.1016/j.phymed.2025.156845
Yu Feng Zhang, Ze Lin Xu, Chen Wang, Jing Li, Meng Ying Wu, Yi Qi Yi, Ting Wang, Po Bian
{"title":"Resveratrol attenuates prenatal X-ray-induced microcephaly and adult depression via SIRT1-mediated senescence suppression and TPH2/5-HT pathway restoration in mice","authors":"Yu Feng Zhang, Ze Lin Xu, Chen Wang, Jing Li, Meng Ying Wu, Yi Qi Yi, Ting Wang, Po Bian","doi":"10.1016/j.phymed.2025.156845","DOIUrl":"10.1016/j.phymed.2025.156845","url":null,"abstract":"<div><h3>Background</h3><div>With increasing use of medical imaging (e.g., CT scans) and environmental radiation sources, over 2 % of pregnancies worldwide are inadvertently exposed to low-dose ionizing radiation (IR), raising urgent concerns about fetal neuroprotection. While prenatal IR is implicated in microcephaly and lifelong neuropsychiatric risks, prior studies have not resolved whether sirtuin-mediated pathways, particularly SIRT1/TPH2 signaling, drive these deficits or whether dietary phytochemicals like resveratrol can mitigate them.</div></div><div><h3>Purpose</h3><div>To determine (1) the role of SIRT1/TPH2 signaling in IR-induced neurodevelopmental and psychiatric impairments, and (2) the therapeutic potential of maternal resveratrol supplementation to counteract these effects—a strategy not previously explored in prenatal radiation models.</div></div><div><h3>Study design</h3><div>Mouse cohorts received prenatal X-ray irradiation (0, 1.0 Gy, 2 Gy gestational day 8) with/without resveratrol supplementation, followed by longitudinal cortical and behavioral analyses.</div></div><div><h3>Methods</h3><div>RNA sequencing/Western blotting quantified SIRT1, TPH2, BDNF, and senescence markers (P16, P21 and SA-β-gal). 5-HT levels were assessed by ELISA. Depression-like behaviors were tested via forced swim and tail suspension.</div></div><div><h3>Results</h3><div>IR-exposed fetuses exhibited progressive microcephaly with reduced cortical thickness, accompanied by SIRT1 downregulation, BDNF suppression, and elevated cellular senescence. Adult offspring displayed depression-like behaviors, linked to TPH2 downregulation and diminished 5-HT levels. Resveratrol supplementation normalized SIRT1/TPH2 signaling, restored cortical neurotrophic factors, and attenuated both microcephaly and depressive phenotypes.</div></div><div><h3>Conclusion</h3><div>This study provides the first evidence that (1) SIRT1/TPH2 signaling is a central mediator of IR-induced neurodevelopmental and psychiatric impairments, and (2) maternal resveratrol supplementation prevents cortical damage and depression in offspring by rescuing this pathway. These findings position resveratrol as a novel, mechanism-driven intervention for fetal neuroprotection against environmental radiation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156845"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PhytomedicinePub Date : 2025-05-21DOI: 10.1016/j.phymed.2025.156890
Baibai Ye , Cheng Lin , Hao Huang , Ping Chen , Xinyu Liu , Keke Wang , Han Zhang , Jiahui Liu , Chenning Zhang , Linfu Li
{"title":"Sophora compounds against non-small cell lung cancer: Research status and mechanisms","authors":"Baibai Ye , Cheng Lin , Hao Huang , Ping Chen , Xinyu Liu , Keke Wang , Han Zhang , Jiahui Liu , Chenning Zhang , Linfu Li","doi":"10.1016/j.phymed.2025.156890","DOIUrl":"10.1016/j.phymed.2025.156890","url":null,"abstract":"<div><h3>Background</h3><div>Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, characterized by dysregulated signaling pathways. Many Sophora compounds exhibit potential anti-NSCLC properties. However, the research status, particularly regarding the underlying mechanisms, remains fragmented.</div></div><div><h3>Purpose</h3><div>To review the research status as well as mechanisms of Sophora compounds against NSCLC.</div></div><div><h3>Methods</h3><div>A systematic review was conducted on publications retrieved from PubMed, Web of Science and CNKI. The retrieval keywords are paired in various forms of \"Sophora compound name\" and \"non-small cell lung cancer\" (including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma). Only experimental (at cell or animal level) or clinical studies demonstrating therapeutic effects of Sophora compounds were included.</div></div><div><h3>Results</h3><div>>52 Sophora compounds have demonstrated potential anti-NSCLC effects through various signaling pathways, primarily targeting apoptosis induction, cell cycle arrest, and metastasis suppression. Investigated signaling pathways mainly include apoptosis, PI3K/Akt/mTOR, MAPK, STAT3/NF-κB, and EGFR signaling. The expression of apoptotic caspases, Bcl-2, Bax, Akt, mTOR, PI3K, Erk, Jnk, p38, STAT3 and NF-κB is frequently assayed. Notably, most researches have focused on cell models of A549 and H1299, primarily on aforementioned signaling pathways at the protein level.</div></div><div><h3>Conclusion</h3><div>Many Sophora compounds, particularly flavonoids, show promise as multi-target agents against NSCLC. However, animal experiments and clinical evidence remain limited, and future studies could prioritize investigations on deeper molecular mechanisms, and on little-explored toxicology.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156890"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PhytomedicinePub Date : 2025-05-21DOI: 10.1016/j.phymed.2025.156889
Tom Ryu , Beom Sun Chung , Jaejun Lee , Ji Won Han , Hyun Yang , Keungmo Yang
{"title":"Protective effects of Ginkgo biloba supplementation on clinical outcomes in metabolic dysfunction-associated steatotic liver disease","authors":"Tom Ryu , Beom Sun Chung , Jaejun Lee , Ji Won Han , Hyun Yang , Keungmo Yang","doi":"10.1016/j.phymed.2025.156889","DOIUrl":"10.1016/j.phymed.2025.156889","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern linked to increased risks of cardiovascular disease, chronic kidney disease (CKD), and premature mortality. Ginkgo biloba has shown potential therapeutic benefits in conditions characterized by metabolic dysfunction. This study aimed to evaluate the potential protective effects of Ginkgo biloba supplementation on overall survival (OS) and the incidence of cardiovascular and renal outcomes specifically in MASLD patients.</div></div><div><h3>Methods</h3><div>This cohort study included 402,476 participants from the UK Biobank, categorized into MASLD and No steatotic liver disease (SLD) cohorts. Ginkgo biloba users and non-users were compared using inverse probability of treatment weighting to balance baseline characteristics. Clinical outcomes were assessed using Cox proportional hazards models, with subgroup analyses.</div></div><div><h3>Results</h3><div>Ginkgo biloba supplementation was associated with significantly improved OS [hazard ratio (HR) = 0.79, 95 % confidence interval (CI): 0.64–0.98, <em>p</em> = 0.034) and reduced risks of cardiovascular events (HR = 0.82, 95 % CI: 0.66–1.00, <em>p</em> = 0.012) and CKD (HR = 0.73, 95 % CI: 0.56–0.96, <em>p</em> = 0.012) in the MASLD cohort, while no significant benefits were observed in the No SLD cohort. Subgroup analyses indicated enhanced benefits in older adults, males, individuals with BMI ≥ 25 kg/m², and diabetic patients. The beneficial effects were pronounced in patients with advanced fibrosis.</div></div><div><h3>Conclusion</h3><div>Ginkgo biloba supplementation is associated with improved survival and reduced cardiovascular and renal risks in MASLD patients, particularly in high-risk subgroups. These findings highlight the potential of Ginkgo biloba as an adjunctive therapy in MASLD management. This is the first large-scale study to examine the potential impact of Ginkgo biloba supplementation on clinical outcomes in MASLD, with fibrosis-stratified analyses providing insights into its differential effects across disease severity.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156889"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PhytomedicinePub Date : 2025-05-20DOI: 10.1016/j.phymed.2025.156883
Li-Ling Jia , Chen-Jie Wu , Pei-Wen Ye , Qian Zhang , Hua Liu , Tu-Ping Li , Xiao-Lei Hu
{"title":"Terrestrosin D promotes autophagy and apoptosis of breast cancer cells through PSMD1-dependent activation of P53 pathway","authors":"Li-Ling Jia , Chen-Jie Wu , Pei-Wen Ye , Qian Zhang , Hua Liu , Tu-Ping Li , Xiao-Lei Hu","doi":"10.1016/j.phymed.2025.156883","DOIUrl":"10.1016/j.phymed.2025.156883","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Breast cancer, particularly triple-negative breast cancer (TNBC), poses a significant threat to women's health. In tumor cells, autophagy and apoptosis are double-edged swords, playing complex roles in cancer progression and treatment. This study aimed to investigate whether Terrestrosin D (TED) exerts antitumor effects on TNBC by modulating autophagy and apoptosis, and to elucidate the underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>The antiproliferative and pro-apoptotic effects of TED on TNBC cells were assessed using CCK-8, EdU assay, Live/Dead staining, and flow cytometry. Autophagy was monitored through immunofluorescence and confocal microscopy. RNA sequencing was performed to identify the pathways and molecular targets involved. The anti-TNBC effects of TED were further evaluated in vivo using tumor xenograft models. Western blotting was conducted to validate the relationship between PSMD1, P53, and TED-induced antitumor activity.</div></div><div><h3>Results</h3><div>TED exhibited significant antitumor effects both in vitro and in vivo. Cellular phenotypic analyses revealed that TED promoted autophagy and apoptosis. Transcriptomic analyses indicated that TED stabilizes P53 expression and activates the P53 signaling pathway by inhibiting the function of PSMD1.</div></div><div><h3>Conclusion</h3><div>TED exhibits potent antitumor effects on TNBC by promoting autophagy and apoptosis. It achieves this through PSMD1 inhibition, stabilizing P53 expression, and activating the P53 pathway. Notably, this study is the first to demonstrate that TED directly targets PSMD1, a key proteasomal regulator, thereby unveiling a novel mechanism for P53 stabilization in TNBC. These findings provide new insights into the therapeutic modulation of the PSMD1 - P53 axis by natural compounds and support the development of TED as a multi-functional agent for aggressive breast cancers.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156883"},"PeriodicalIF":6.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}